Loratadine Claritin

Ball-and-Stick Model

MOLECULES AND MEDICINE Structural Formula

= Carbon = Hydrogen A = Oxygen £ = Chlorine A = Nitrogen

Year of discovery: 1981; Year of introduction: 1993 (Schering-Plough); Drug category: Long-acting second generation antihistamine; Main uses: Relieve the symptoms of seasonal allergies and rashes caused by food allergies; Other brand names: Claratyne (Schering-Plough), Alavert (Wyeth); Related drugs: Acrivastine (Semprex-D), Cetirizine (Zyrtec), Fexofenadine (Allegra).

Allergy, the immune system's misguided response to foreign substances that are normally harmless, affects about 50 million people and is the sixth leading cause of chronic illness in the United States. The most common type of allergy arises from hypersensitivity of the upper respiratory tract to airborne allergens, which can cause runny nose, itching of the nose and throat, and coughing. Certain foods such as tree nuts, peanut and shellfish as well as medicines can also act as allergens, leading to rash, vomiting, diarrhea, urticaria, and swelling. Other allergens occur in certain materials for instance in latex rubber. Extreme allergic reactions affect many organs. This response typically occurs when the allergen is eaten or injected (for example a bee sting) into an already hypersensitized person and is termed anaphylaxis.

In allergic reactions, the immune system which normally functions as the body's main line of defense against microbes, reacts to the allergens as harmful substances. Upon first contact with the allergen, the immune system generates large amounts of immunoglobulin E (IgE), a type of antibody that binds tightly to mast cells in the connective tissue and basophil cells in the blood. Upon further exposure, the allergen attaches to IgE on the surface of mast cells and basophils, triggering the release of powerful mediators including histamine, prostaglandins and leukotrienes, which are inflammatory (see page 41).

In 1910, a factor in tissue extracts that stimulates the contraction of smooth muscle was discovered by H. Dale and P. Laidlaw. Seventeen years later, C. Best purified this factor from lung and liver samples and identified it as histamine, a molecule formed by loss of C02 from the amino acid histidine.

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Histidine

-co2

Histamine

The first histamine blocker was described in 1937 by D. Bovet and A. Staub, who screened a series of synthetic amines for antihistamine activity. One of the substances effectively protected guinea pigs against lethal doses of histamine, but it was too toxic for clinical use. By 1944, Bovet and coworkers discovered pyrilamine maleate, which is one of the most effective antihistamines.

Pyrilamine

Although still commercially available, it is not generally used since it causes drowsiness, because it penetrates the brain, which has histamine receptors. In the following decades, several antihistamine drugs were developed that do not produce sedation. Loratadine (Claritin), developed by Schering-Plough in 1981, became the most widely used. Since 2002 it has been available without a prescription and as a generic drug. The antihistamines used to treat allergy bind to the H-1 histamine receptor whereas those used to reduce gastric acidity bind to another histamine receptor, H-2 (see page 103).1,2

1. Clin. Exp. Allergy 1998, 28, 15-19; 2. Drugs 1999, 57, 3147; Refs. p. 82

TYPE2 DIABETES

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